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Updated: Oct 21, 2025

Visualization of Endogenous Mitophagy Complexes In Situ in Human Pancreatic Beta Cells Utilizing Proximity Ligation Assay
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Visualization of Endogenous Mitophagy Complexes In Situ in Human Pancreatic Beta Cells Utilizing Proximity Ligation Assay

Published on: May 2, 2019

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Deathly triangle for pancreatic β-cells: Hippo pathway-MTORC1-autophagy

Amin Ardestani1,2, Kathrin Maedler1

  • 1Centre for Biomolecular Interactions Bremen, University of Bremen, Bremen, Germany.

Autophagy
|September 2, 2021
PubMed

Insights

A key cellular loop involving LATS2, MTORC1, and autophagy regulates pancreatic beta-cell survival in type 2 diabetes. Chronic stress impairs this loop, leading to beta-cell failure and death.

Area of Science:

  • Cell Biology
  • Endocrinology
  • Metabolic Diseases

Background:

  • Progressive decline in macroautophagic/autophagic flux is a hallmark of pancreatic beta-cell failure in type 2 diabetes (T2D).
  • Intrinsic factors and molecular mechanisms driving this decline remain incompletely understood.

Purpose of the Study:

  • To elucidate the molecular mechanisms regulating pancreatic beta-cell survival and adaptation under metabolic stress.
  • To investigate the role of the Hippo pathway kinase LATS2, MTORC1, and autophagy in T2D pathogenesis.

Main Methods:

  • The study focused on a stress-sensitive cellular loop involving LATS2, MTORC1, and autophagy.
  • Mechanisms of interaction and regulation between these components were investigated in the context of beta-cell function.

Main Results:

  • Chronic metabolic stress leads to LATS2 hyperactivation, inducing MTORC1, impairing autophagic flux, and causing beta-cell death.
  • Autophagy reciprocally controls beta-cell survival by lysosomal degradation of LATS2 under physiological conditions.

Conclusions:

  • The interplay between autophagy and LATS2 is crucial for regulating beta-cell turnover and functional compensation during metabolic stress.
  • Dysregulation of this loop contributes to beta-cell failure in type 2 diabetes.
Keywords:
AutophagyLATS2MTORC1beta cellsdiabetestype 2 diabetes

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